Toward individualized medicine in stroke—The TiMeS project: Protocol of longitudinal, multi-modal, multi-domain study in stroke

Abstract

Despite recent improvements, complete motor recovery occurs in <15% of stroke patients. To improve the therapeutic outcomes, there is a strong need to tailor treatments to each individual patient. However, there is a lack of knowledge concerning the precise neuronal mechanisms underlying the degree and course of motor recovery and its individual differences, especially in the view of brain network properties despite the fact that it became more and more clear that stroke is a network disorder. The TiMeS project is a longitudinal exploratory study aiming at characterizing stroke phenotypes of a large, representative stroke cohort through an extensive, multi-modal and multi-domain evaluation. The ultimate goal of the study is to identify prognostic biomarkers allowing to predict the individual degree and course of motor recovery and its underlying neuronal mechanisms paving the way for novel interventions and treatment stratification for the individual patients. A total of up to 100 patients will be assessed at 4 timepoints over the first year after the stroke: during the first (T1) and third (T2) week, then three (T3) and twelve (T4) months after stroke onset. To assess underlying mechanisms of recovery with a focus on network analyses and brain connectivity, we will apply synergistic state-of-the-art systems neuroscience methods including functional, diffusion, and structural magnetic resonance imaging (MRI), and electrophysiological evaluation based on transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG) and electromyography (EMG). In addition, an extensive, multi-domain neuropsychological evaluation will be performed at each timepoint, covering all sensorimotor and cognitive domains. This project will significantly add to the understanding of underlying mechanisms of motor recovery with a strong focus on the interactions between the motor and other cognitive domains and multimodal network analyses. The population-based, multi-dimensional dataset will serve as a basis to develop biomarkers to predict outcome and promote personalized stratification toward individually tailored treatment concepts using neuro-technologies, thus paving the way toward personalized precision medicine approaches in stroke rehabilitation.

Brain oscillatory modes as a proxy of stroke recovery

“…We studied the changes in brain oscillatory modes unveiled from TMS-induced oscillations and determined their importance for residual motor functions and recovery. The present analyses are based on a large dataset from the TiMeS protocol (51) , a multimodal, multidomain, longitudinal evaluation of stroke patients from the acute to the subacute and early-chronic stage. We used the PARAFAC approach to extract brain oscillatory modes and to study their disruption with respect to motor impairment at the acute stage of stroke as well as changes during the course of motor recovery.…”

Stroke Recovery–Related Changes in Cortical Reactivity Based on Modulation of Intracortical Inhibition

“…For more details on the protocol and analysis, the reader might refer to the Supplemental Material and Fleury et al 18…”

“…7 Here, we longitudinally evaluated (acute to late subacute) a cohort of patients with stroke with TMS-EEG, in the framework of the TiMeS project. 18 The present study specifically focused on the analysis of the TMS-evoked responses and complements the study of TMS-induced oscillations, 19 the results of which will be put into perspective with those of the present study. Complementary TMS-EEG readouts enabled the study of cortical excitability and evoked dynamics from the individuals' brain reactivity, and their association with motor function at each stage and during the process of motor recovery.…”

MEP and TEP features variability: is it just the brain-state?

“…The dataset was acquired in the framework of the TiMeS project, of which the full protocol can be found at [47]. TMS-EEG experiments were run with 18 healthy young right-handed participants (7 females, 27.0 ± 2.8 years old).…”